血管紧张素原基因启动子区域单核苷酸多态与高血压并发冠心病的关系

目的　研究在中国南方汉人群中 ,血管紧张素原基因 (angiotensinogen ,AGT)启动子区域 2 17位和 2 0位上的二种单核苷酸多态与高血压病 (EH)并发冠心病的关系。方法　运用多重SNaPshot反应 ,对 2 0 5例EH并发冠心病患者、185例EH患者和 185名健康对照者进行G 2 17A和A 2 0C多态基因分型。结果　G 2 17A多态的基因型分布在EH并发冠心病组 (AA =8、AG =71、GG =12 6 )和对照组 (AA =8、AG =37、GG =14 0 )之间有显著性差异 (P =0 0 0 5 ) ;A、G等位基因频率与对照组相比亦有显著性差异 (A 2 1 2 2 %、G 78 78%比A 14 32 %、G 85 6 8% ,P =0 0 12 ) ;A 2 0C多态的基因型分布 (CC、AC、AA)及C、A等位基因频率在二组间的差异无显著性 (分别为CC =5、AC =4 9、AA =15 1比CC =2、AC =6 1、AA =12 2 ,P =0 0 97;C 14 39%、A 85 6 1%比C 17 5 7%、A 82 4 3% ,P=0 2 2 6 )。在男性EH并发冠心病组中 ,G 2 17A和A 2 0C多态的基因型分布及其等位基因频率与对照组相比均有显著性差异 (G 2 17A :AA =7、AG =5 3、GG =86比AA =6、AG =2 8、GG =97,P =0 0 2 2 ;A 2 2 95 %、G 77 0 5 %比A 15 2 7%、G 84 73% ,P =0 0 2 2。A 2 0C :CC =3、CA =2 7、AA =116比CC =2、CA =4 3、AA =86 ,P =0 0 2 3;C 11 30 %     

血管紧张素原基因核心启动子区域的单核苷酸多态与冠心病的关系

目的:在中国南方汉族人群中,检测血管紧张素原基因(AGT)5'端核心启动子内AGCE1区域的单 核苷酸多态(SNPs),并探讨其与冠心病发病的关系。方法:应用PCR直接测序技术检测AGCE1区域的序列,并 结合多重SNaPshot反应在145例血压正常的冠心病患者和185例健康对照者中对所检测的SNPs进行基因分 型。结果:在AGT基因AGCE1区域-20和-6位上发现2个SNPs,且A 20C和G 6A多态呈连锁不平衡。A 20C多态的基因型分布在冠心病组(CC=4,AC=29,AA=112)和对照组(2,61,122)之间差异有统计学意义(P <0.05)。C等位基因频率在两组间虽有差异(12.76%/17.57%),但未达到统计学意义(P>0.05)。G 6A多态 的基因型分布和等位基因频率在冠心病组与对照组之间差异均无统计学意义。单倍型分析表明,各组单倍型的 频率分布在两组间差异亦无统计学意义。结论:AGT基因的A 20C多态可能与血压正常人群的冠心病发病相 关。     

血管紧张素转换酶和血管紧张素原基因多态性与冠心病的关系

目的探讨血管紧张素转换酶（ACE）插入／缺失（I／D）多态性和血管紧张素原（AGT）M235T基因多态性与冠心病（CHD）的关系。方法应用多聚酶链反应结合限制性内切酶法（PCR—RFLP）对110例冠心病患者、62例冠状动脉造影正常者以及18名门诊常规体检无冠心病史者基因多态性进行分析。结果①CHD组ACE基因DD基因型及D等位基因频率明显高于健康对照组（分别为43．6％、60．5％比26．3％、44．4％）,差异有统计学意义‘P〈0．05）。CHD组AGT基因TT基因型及T等位基因频率明显高于对照组（分别为66．4％、78．6％比42．5％、60．6％）,差异有统计学意义（尸〈0．05）。②男性CHD组ACE基因DD基因型和D等位基因频率以及AGT基因TT基因型和T等位基因频率均显著高于对照组（均P〈O．05）。女性CHD组ACE基因DD基因型和D等位基因频率以及AGT基因‘rr基因型和T等位基因频率与对照组比较差异无统计学意义（P〉0．05）。③联合分析ACEDD型及AGTTr型罹患冠心病的相对风险,其比数~L（OR）为4．904,高于单基因ACEDD型（2．175）及AGTTT型（2．669）。结论ACE基因I／D多态性及AGT基因M235T多态性与CHD有显著相关性,同时具有ACEDD型及AGT TT型发生冠心病的相对风险显著高于单基因ACEDD型及单基因AGT‘丌型。性别也可作为冠心病的危险因素。     

血管紧张素原基因启动子区域单核苷酸多态性与心肌梗死的相关性

为研究血管紧张素原基因启动子区域 - 2 17、- 2 0位和 - 6位上的三种单核苷酸多态性与心肌梗死的相关性 ,采用多重SnaPshot反应 ,在中国南方汉人群中 ,对 2 16例心肌梗死患者和 185名健康对照者进行G 2 17A ,A 2 0C和G 6A多态基因分型。结果发现 ,G 2 17A多态AA、AG和GG基因型分布和A、G等位基因频率在心肌梗死组与对照组之间相比有显著性差异 (分别为 10、77、12 9比 8、37、14 0 ,P =0 .0 0 2 ;2 2 .4 5 %、77.5 5 %比 14 .32 %、85 .6 8% ,P=0 .0 0 3)。G 6A多态AA、AG和GG基因型分布在心肌梗死组和对照组之间亦有显著性差异 (分别为 14 7、6 4、5比12 7、4 4、14 ,P =0 .0 2 9) ,但A、G等位基因频率在两组间无显著性差异 (P =0 .394 )。A 2 0C多态CC、AC和AA基因型分布在两组间有差异 (分别为 6、5 1、15 9比 2、6 1、12 2 ) ,但无统计学意义 (P =0 .0 6 7) ,C、A等位基因频率在两组间亦无显著性差异 (P >0 .0 5 )。Logistic回归分析发现 ,年龄 (P =0 .0 0 1)、收缩压 (P =0 .0 13)和血浆甘油三酯浓度 (P =0 .0 10 )是该人群发生心肌梗死的独立危险因素 ,而高密度脂蛋白胆固醇 (P =0 .0 18)是一种保护因素。结果提示 ,在中国南方汉人群中 ,血管紧张素原基因G 2 17A和G 6A多态可能与心肌梗死的发生     

血管紧张素原基因多态性与心血管疾病

血管紧张素原(AGT)基因的多态性与心血管病的研究很多,但二者的关系复杂且不同的研究所得结果也不一致。本文综述了AGT基因的多态性与肥厚型心肌病、二尖瓣脱垂、心房颤动、高血压病及冠心病关系的研究概况。     

血管紧张素原基因和血管紧张素转换酶基因多态性与高血压

目的　研究中国人群中血管紧张素原 (AGT)基因单核苷酸多态性 (SNP)及血管紧张素转换酶 (ACE)基因插入 /缺失多态与高血压病的关系。方法　在 3 4 5例高血压病患者与 2 0 6名血压正常人中采用PCR RFLP法检测AGT基因A 2 0C ,A 6G和M 2 3 5T的多态性 ,用PCR法检测ACE基因 16内含子Alu片段插入 /缺失多态 ,同时用EM算法进行两位点连锁不平衡分析。结果　在M 2 3 5T和A 2 0C ,M 2 3 5T和A 6G ,A 2 0C和A 6G位点观察到了连锁不平衡 (P <10 - 4)。病例 对照检验显示T2 3 5等位基因频率在高血压组中高于对照组 ,且高血压病患者中ACE (DD +ID) +AGT TT2 3 5基因型频率高于对照组。结论　受检人群中AGT基因各多态频率处于两两连锁不平衡 ,但AGT基因即T2 3 5位点以隐性作用方式与高血压关联 ,T2 3 5等位基因与ACE D等位基因在高血压病发生中具协同作用     

老年人心肌梗死与血管紧张素原基因T174M多态性关系

目的 探讨血管紧张素原（angiotensinogen，AGT）基因T174M变异与老年人心肌梗死（MI）的发病关系。方法 采用聚合酶链反应（PCR）、限制性片段长度多态性（RFLP）分析，对55例呈MI患者和60例无冠心病证据的对照组（老年人）进行AGT基因T174M等位基因检测。结果 MI患者AGT基因174MM型（7．27％）和M174等位基因（16．36％）的频率显著高于健康对照组（分别为1．67％和9．17％，X^2=7．55，P=0．022，X^2=5．79，P=0．016），经校正冠心病的主要危险因素后，AGT基因174MM仍可显著增加心肌梗死发生的危险性（比数比3．66，P=0．018）。结论 AGT基因T174M可能是老年人MI发病的重要危险因素之。     

血管紧张素原基因M235T多态性与心血管疾病

近年来,越来越多的研究结果表明血管紧张素原基因M235T多态性与心血管疾病密切相关,通过对二者关系的研究,我们可以从分子水平上探讨心血管疾病的病因,从而为心血管疾病的防治提供新的思路。现对这一研究现状作一综述。     

血管紧张素转换酶和血管紧张素原基因多态与心肌梗死相关性的研究

目的　探讨血管紧张素转换酶 (ACE)和血管紧张素原 (AGT)基因多态与中国北方人群中心肌梗死 (MI)发病的相关性。方法　采用聚合酶链反应 (PCR)和酶切方法对 90例正常对照者和 6 5例MI患者的ACE插入 /缺失(I/D)多态 ,AGT的M2 35T多态进行检测。结果　MI患者中ACE基因的DD基因型频率 0 431明显高于对照组0 15 6 (P <0 0 1) ,D等位基因频率 0 5 91高于对照组 0 333(P <0 0 1) ,MI患者中AGT基因的TT基因型频率0 6 92高于对照组 0 5 6 7(P <0 0 5 )。结论　DD基因型和TT基因型与中国北方人群心肌梗死相关 ,提示它们是心肌梗死的危险因子。     

中国苗族人群血管紧张素原和血管紧张素转化酶基因多态性与冠心病的关系

目的 研究血管紧张素原(ACT)基因M235T分子变异和血管紧张素转化酶(ACE)基因I/D多态性与冠状动脉粥样硬化的关系.方法 采用聚合酶链反应一限制性片段长度多态性(PCR-RFLP)技术检测冠心病(CHD)组151例和正常对照组127例AGT基因多态性,采用聚合酶链反应技术检测CHD组151例和正常对照组127例ACE基因I/D多态性.结果 CHD组AGT-TT基因型频率为76.26%,显著高于对照组44.10%(P<0.01).ACE-DD基因型频率为35.10%,显著高于对照组14.96%(P<0.01).结论 在中国苗族人群中,AGT基因TT基因型和AGE基因DD基因型是CHD发病既相互独立又具有协同作用的危险因子.     

Association between T174M polymorphism in the angiotensinogen gene and risk of coronary artery disease: a meta-analysis

Background Angiotensinogen (AGT) T174M gene polymorphism has been suggested to be linked to risk of coronary artery disease, however, results from studies of this association have been inconsistent. In this study, we assess the relationship between AGT T174M gene polymorphism and coronary artery disease. Methods We conducted a meta-analysis of 18 case-control studies with 8,147 coronary artery disease cases and 5,344 controls in Google scholar, PubMed, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases to identify eligible studies published by July, 2012. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated from these studies. Results Overall, a significant association was found between angiotensinogen T174M polymorphism and coronary artery disease risk when all studies were pooled into the meta-analysis (TT vs. MM: OR = 0.53, 95% CI = 0.40–0.71; dominant model: OR = 1.16, 95% CI = 1.01–1.35; recessive model: OR = 0.54, 95% CI = 0.40–0.72). In a stratified analysis, the results indicate a significant associa?tion in Caucasians suffering from coronary stenosis (TT vs. MM: OR = 0.38, 95% CI = 0.23–0.63; recessive model: OR = 0.39, 95% CI = 0.23–0.64). No significant increased risk for coronary artery disease was found in Asians. Conclusions The meta-analysis indicate a significant associa?tion of T174M polymorphism with coronary stenosis risk in Caucasians.     

基因芯片技术分析老年冠心病患者的易感基因

目的 研究血管紧张素转换酶（ACE）、血管紧张素原（AGT）及内皮型一氧化氮合酶（eNOS）基因多态性与老年人冠心病（CHD）的关系.方法 选择老年CHD患者100例及对照者91例,应用基因芯片技术检测ACE、AGT和eNOS基因多态性,并比较其基因型及等位基因频率。结果 CHD组ACE DD基因型频率（28.0%）与对照组（15.4%）比较，差异有统计学意义（P＜0.05）,ACE基因多态性与老年CHD相关.AGT TT基因型频率（75.0%）与对照组（51.7%）比较，差异有统计学意义（P＜0.01）,AGT基因多态性与老年CHD相关.eNOS TT基因型频率（5.0%）与对照组（0.0%）比较,差异无统计学意义（P＞0.05）。同时携带ACE DD和AGT TT基因型或AGT TT和eNOS TT基因型者与老年CHD呈显著正相关（OR=2.9,P＜0.05,OR=1.1,P＜0.05）。结论 ACE和AGT基因多态性可能是中国老年人CHD的危险因素。     

DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency

Coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. In this study, we investigated the effects of the XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on the presence and the severity of CAD. We also investigated the presence of DNA damage in the peripheral lymphocytes of patients with CAD by using the micronucleus (MN) test and the effect of XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on this damage. The study population consisted of 147 patients with angiographically documented CAD and 48 healthy controls. No association between XPD Lys751Gln or XRCC1 Arg399Gln polymorphisms and the presence or the severity of CAD was observed. On the other hand, a significantly higher frequency of MN was observed in CAD patients compared with controls (5.7 ± 1.9 vs 5.0 ± 2.1, respectively, P = 0.018). We found an elevated frequency of MN in CAD patients with the XPD 751Gln allele (Gln/Gln genotype) or the XRCC1 399Gln (Arg/Gln or Gln/Gln genotypes) allele compared with the XPD 751Lys (Lys/Lys genotype) allele or XRCC1 399 Arg (Arg /Arg genotype) allele, respectively. These preliminary results suggest that XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms may not be a significant risk factor for developing CAD. In addition, our results indicate that the MN frequency is associated with presence, but not severity, of CAD and is related to the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms, suggesting an elevated frequency of MN in CAD patients with the XPD 751Gln or XRCC1 399Gln alleles.     

Association between inflammatory gene polymorphisms and coronary artery disease in an Indian population

Background Inflammation is one of the major components of atherosclerosis which is the underlying disorder that leads to various diseases including coronary artery disease (CAD). Genes that are involved in the inflammatory processes are therefore good candidates for the risk of CAD. Variations in the genes involved in various molecular pathways of inflammation have been implicated to exaggerated atherosclerosis and the risk of cardiovascular diseases. In this study, we performed a genetic association study on the single nucleotide polymorphisms (SNPs) present in the genes CD14 (−159 C/T), TNFα (−308 G/A), IL-1α (−889 C/T), IL-6 (−174 G/C), PSMA6 (−8 C/G), and PDE4D (SNP83 T/C, respectively) in order to discern their possible role in the susceptibility to CAD in a North Indian population. Methods Angiographically proven CAD patients (n = 210) and age, sex and ethnically matched normal healthy controls (n = 232) were recruited for this case-control study. Genotypes were determined by PCR–RFLP method. Chi-square and logistic regression analyses were performed to compare the genotype and allele frequencies between the patient and the control groups. Results None of the SNPs showed significant association with CAD in the study population before and after adjustment for the confounding risk factors like age, sex, hypertension, smoking habit, and diabetes. Conclusion This study was unable to demonstrate any association between the six gene variants tested and CAD in the North Indian population.     

Synergistic effects between 561A > C and 98G > T polymorphisms of E-selectin gene and hypercholesterolemia in determining the susceptibility to coronary artery disease

Coronary artery disease (CAD) is a multifactorial disease that results from the interaction between genetic and traditional risk factors. The endothelium dysfunction plays a key role in the progression of atherosclerotic lesions. E-selectin is a marker of endothelium dysfunction. The aim of the present study was to find a relationship between 561A > C and 98G > T polymorphisms of E-selectin gene and CAD as well as interactions between these polymorphic variants and traditional risk factors of the disease in determining the susceptibility to CAD. The study population included 191 patients with angiographically documented CAD and 203 blood donors. The analysis of genetic polymorphisms was performed using the polymerase chain reaction-restriction fragment length polymorphism method. We found that the frequencies of 561C and 98T alleles of E-selectin gene and carriers of C and T alleles were similar in the entire groups as well as in the age-and sex-matched subgroups. We observed a strong significant correlation between those two polymorphisms; almost all subjects possessing one "proatherosclerotic" allele of E-selectin gene also had the second allele (r = 0.963, P < 0.0001). There were also synergistic effects between both polymorphisms and hypercholesterolemia (but not with smoking or overweight) in determining the susceptibility to CAD. The present study points to synergistic interactions between 561A > C or 98G > T polymorphisms of E-selectin gene and hypercholesterolemia that cause a significant increase in the susceptibility to CAD.     

白细胞介素-6基因多态性对冠心病发病易感性的影响及其机制

目的了解白细胞介素-6（IL-6）基因-597G／A及-572C／G多态性对冠心病（CHD）发病易感性的影响及其影响机制。方法 应用聚合酶链反应．限制性片段长度多态性（PCR-RFLP）分析方法,测定245例CHD患者和260例正常对照者的IL-6基因型,探讨其与CHD的相关关系;观察基因型对血清IL-6水平的影响,并采用logistic回归分析法了解基因型与CHD其他危险因素间的相互作用。结果 两组研究对象中-597位点均仅发现GG基因型。-572C／G基因型和等位基因频率在两组间存在明显统计学差异（P均〈0．01）,CHD组GG基因型和G等位基因频率均显著高于对照组（P均〈0．01）;CG、GG基因型人群患CHD的风险分别为CC基因型人群的1．46倍（95％CI：1．01～2．10,P〈0．05）和5．19倍（95％CI：1．69～15．89,P〈0．01）;不同基因型患者间血清IL-6水平无统计学差异（P〉0．05）;-572C／G基因型与总胆固醇、甘油三酯间存在一定的交互作用,OR值分别为1．76（95％CI：1．05～3．16,P〈0．05）、2．51（95％CI：1．04～6．45,P〈0．05）。结论 IL-6基因-597G／A多态性可能与中国汉族人群CHD发病易感性无关,而-572C／G多态性可能是该人群CHD发病的易感基因之一,其可能通过对组织IL-6水平的影响及与血脂的协同作用参与CHD的发生。     

基因芯片技术分析与冠心病的相关基因

目的评估血管紧张素原(angiotensinogen,AGT)、内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)和载脂蛋白E(apolipoprotein E,ApoE)多态性与冠心病的关系,并分析AGT、eNOS和ApoE基因多态性在冠心病的发生和发展中是否存在协同作用。方法选择冠心病患者133例及对照者154名,用基因芯片技术检测AGT、eNOS和ApoE基因多态性,并对比其基因型及等位基因频率。结果冠心病组AGT TT和eNOS TT基因型频率与对照组相比差异有统计学意义,分别为OR=2．63,P<0．001,OR=8．50,P< 0．05。AGT和eNOS基因多态性与冠心病相关。同时携带AGT TT和eNOS TT基因型者与冠心病密切相关(OR=1．05,P<0．01)。ApoE基因型频率及等位基因频率与对照组相比差异无统计学意义(P>0．05)。结论AGT和eNOS基因多态性可能是中国人冠心病的危险因素,基因芯片技术为研究多种易感基因与冠心病的相关性提供了一项高效、敏感的方法。     

冠心病患者对氧磷酯酶1基因多态性分析

目的 :探讨冠心病 (CHD)患者对氧磷酯酶 1(Paraoxonase 1,PON1)基因多态性与血脂的关系及其病因学意义。方法 :使用Taqman特异性等位基因鉴别法检测 93例CHD患者和 138例健康对照者的基因组DNA ,测定该基因G 12 6C、L5 5M和Q192R三个多态性的基因型和由三个位点的等位基因组成的单体型。统计分析两组间这些基因型和单体型频率分布差异性 ,以及不同基因型与血脂水平的相关性。结果 :CHD患者中Q192R位点的QQ基因型携带者明显少于健康对照者 (7.5 %∶18.1% ,P <0 .0 5 ) ,各种单体型在两组间差异无显著性意义。各基因型之间血脂水平差异亦无显著性意义。结论 :PON1基因中只有Q192R多态性与CHD的发病相关